tbuckley/cabot-search huggingface dataset:
SEDDS-loaded mucoadhesive fiber patches for advanced oromucosal delivery of poorly soluble drugs
Authors: Julian David Friedl, Marcel Walther, Pia Katharina Vestweber, Jana Wächter, Patrick Knoll, Arne Matteo Jörgensen, Andreas Bernkop-Schnürch, Maike Windbergs
Journal: Journal of Controlled Release (2022)

To date, buccal administration of lipophilic drugs is still a major challenge due to their poor solubility in saliva and limited penetration into mucosal tissues. To overcome these limitations, we developed electrospun patches combining the benefits of mucoadhesive fibers and self-emulsifying drug delivery systems (SEDDS). The fiber system comprises a combination of mucoadhesive thiolated polyacrylic acid fibers and SEDDS-loaded fibers fabricated by parallel electrospinning. The resulting mucoadhesive electrospun SEDDS patches were systemically investigated for fiber characteristics, self-emulsification, mucoadhesion, drug penetration into porcine buccal tissue and biocompatibility. The patches showed high encapsulation efficiency for SEDDS without causing fiber defects or leakage. SEDDS incorporation enhanced the spinning process and reduced the fiber diameter and fiber size distribution. Hydration-dependent self-emulsification provided a controlled release of curcumin being encapsulated in nano-scaled o/w emulsion for over 3 h. Due to the thiolated polyacrylic acid fibers, the buccal residence time of patches was 200-fold prolonged. Further, they promoted a significantly increased drug penetration into buccal tissue compared to fiber patches without SEDDS. Finally, biocompatibility and improved therapeutic effects of curcumin-loaded patches on human keratinocytes and fibroblasts were confirmed. Mucoadhesive electrospun SEDDS patches represent a promising approach to overcome current challenges in the oromucosal delivery of lipophilic drugs to unlock their full therapeutic potential.
Diagnostic and Surgical Treatment of Multi-Valve Heart Disease with Infective Endocarditis
Authors: Abdumadjidov H. A
Journal: Clinical Cardiology and Cardiovascular Interventions (2022)

" Diagnostic and surgical treatment of multi-valve heart disease with infective endocarditis" Objective: The aim of the study was to analyze our own experience of diagnosis, choice of tactics and execution of multi-valve surgical correction of heart defects in infective endocarditis (IE). Methods: We retrospectively analyzed data and clinical results of 156 patients with infective endocarditis who underwent the cardiac surgery in our clinic. Among them, 85 were men (56.5%), and women - 71 (45.5%). Age of our patients ranged from 12 to 68 (mean 32.76 (1.6)) years. The patients were divided into 2 groups: group 1, 89 (57.4%) patients who underwent a complex of developed by the author’s antibiotic therapy, surgical treatment and preventive measures and 2-group 67 (42.6%) patients who underwent the traditional surgical treatment scheme. We analyzed electrocardiography, chest X-Ray, transthoracic echocardiography, transesophageal echocardiography, cardiac catheterization and coronary angiography and blood culture analysis. Results: Intraoperative treatment - preventive measures (TPM) were as follows; mechanical and chemical sanitation of the infected area of the heart; implantation of valves with antibacterial properties; hyperthermic perfusion; antimicrobial therapy, including anti-fungal agents. Application of the above measures reduced mortality in the study group to 5.1%, in the control group - 9.3%. In dynamics, mortality declined to 3.9% in the study group. Conclusion: Our results of surgical treatment of multi-valve heart defects with infective endocarditis showed the efficacy of developed complex preoperative and intraoperative measures in surgical treatment of IE. This new treatment approach is associated with significant improvement of left ventricular function and low mortality rate.
Re: Benjamin Pradere, Richard Mallet, Alexandre de La Taille, et al. Climate-smart Actions in the Operating Theatre for Improving Sustainability Practices: A Systematic Review. Eur Urol. In press. https://doi.org/10.1016/j.eururo.2022.01.027
Authors: Michael Baboudjian, Pietro Diana, Alberto Breda
Journal: European Urology (2022)
Soluble TREM2 levels reflect the recruitment and expansion of TREM2+ macrophages that localize to fibrotic areas and limit NASH
Authors: Tim Hendrikx, Florentina Porsch, Máté G Kiss, Dragana Rajcic, Nikolina Papac-Miličević, Constanze Hoebinger, Laura Goederle, Anastasiya Hladik, Lisa E Shaw, Hauke Horstmann, Sylvia Knapp, Sophia Derdak, Martin Bilban, Lena Heintz, Marcin Krawczyk, Rafael Paternostro, Michael Trauner, Matthias Farlik, Dennis Wolf, Christoph J Binder
Journal: Journal of Hepatology (2022)
Update on Guidelines for the Prevention of Cancer-Associated Thrombosis
Authors: Amro Elshoury, Jordan K. Schaefer, Ming Y. Lim, Deidre P. Skalla, Michael B. Streiff
Journal: Journal of the National Comprehensive Cancer Network (2022)

Patients with cancer are at high risk of developing arterial and venous thromboembolism (VTE). They constitute 15% to 20% of the patients diagnosed with VTE. Depending on the type of tumor, cancer therapy, and presence of other risk factors, 1% to 25% of patients with cancer will develop thrombosis. The decision to start patients with cancer on primary thromboprophylaxis depends on patient preference, balancing risk of bleeding versus risk of thrombosis, cost, and adequate organ function. Currently, guidelines recommend against the use of routine primary thromboprophylaxis in unselected ambulatory patients with cancer. Validated risk assessment models can accurately identify patients at highest risk for cancer-associated thrombosis (CAT). This review summarizes the recently updated NCCN Guidelines for CAT primary prophylaxis, with a primarily focus on VTE prevention. Two main clinical questions that providers commonly encounter will also be addressed: which patients with cancer should receive primary thromboprophylaxis (both surgical and medical oncology patients) and how to safely choose between different anticoagulation agents.
Evaluation of Obesity Trends Among US Adolescents by Socioeconomic Status, 1999-2018
Authors: Ryunosuke Goto, Roch Nianogo, Yusuke Okubo, Kosuke Inoue
Journal: JAMA Pediatrics (2022)

This cross-sectional study uses data from the National Health and Nutrition Examination Surveys to evaluate obesity trends among US adolescents from 1999 to 2018, stratified by household income and head of household education level.
Socioeconomic Status and Risk of Bleeding After Mechanical Aortic Valve Replacement
Authors: Magnus Dalén, Michael Persson, Natalie Glaser, Ulrik Sartipy
Journal: Journal of the American College of Cardiology (2022)

Whether low socioeconomic status (SES) is associated with increased risk of anticoagulation-related adverse events in patients with mechanical heart valves is unknown. This study sought to investigate the impact of patients' SES on the risk of bleeding after mechanical aortic valve replacement (AVR). This nationwide population-based cohort study included all patients aged 18-70 years who underwent mechanical AVR in Sweden from 1997 to 2018. Data were obtained from the SWEDEHEART register and other national health data registers. The exposure was quartiles of household disposable income. The primary outcome was hospitalization for a bleeding event. Among 5974 patients, the absolute risk for bleeding after 20 years of follow-up was 20% (95% CI: 17%–24%) in the lowest income quartile (Q1) and 16% (95% CI: 13%–20%) in the highest quartile (Q4). The risk of bleeding decreased with increasing income level and was significantly lower in patients in income level Q3 (HR: 0.77; 95% CI: 0.60–0.99) and Q4 (HR: 0.68; 95% CI: 0.50–0.92) than Q1. The risk of death from intracranial hemorrhage was five times higher in the lowest income quartile than the age- and sex-matched general Swedish population (standardized mortality ratio: 5.0; 95% CI: 3.3–7.4). We observed a strong association between SES and risk of bleeding among patients who underwent mechanical AVR. These findings suggest suboptimal anticoagulation treatment in patients with lower SES and the need for strategies to optimize anticoagulation treatment in patients with a mechanical heart valve. (Health-Data Register Studies of Risk and Outcomes in Cardiac Surgery [HARTROCS]; NCT02276950)
PrecisionFDA Truth Challenge V2: Calling variants from short and long reads in difficult-to-map regions
Authors: Nathan D. Olson, Justin Wagner, Jennifer McDaniel, Sarah H. Stephens, Samuel T. Westreich, Anish G. Prasanna, Elaine Johanson, Emily Boja, Ezekiel J. Maier, Omar Serang, David Jáspez, José M. Lorenzo-Salazar, Adrián Muñoz-Barrera, Luis A. Rubio-Rodríguez, Carlos Flores, Konstantinos Kyriakidis, Andigoni Malousi, Kishwar Shafin, Trevor Pesout, Miten Jain, Benedict Paten, Pi-Chuan Chang, Alexey Kolesnikov, Maria Nattestad, Gunjan Baid, Sidharth Goel, Howard Yang, Andrew Carroll, Robert Eveleigh, Mathieu Bourgey, Guillaume Bourque, Gen Li, ChouXian Ma, LinQi Tang, YuanPing Du, ShaoWei Zhang, Jordi Morata, Raúl Tonda, Genís Parra, Jean-Rémi Trotta, Christian Brueffer, Sinem Demirkaya-Budak, Duygu Kabakci-Zorlu, Deniz Turgut, Özem Kalay, Gungor Budak, Kübra Narcı, Elif Arslan, Richard Brown, Ivan J. Johnson, Alexey Dolgoborodov, Vladimir Semenyuk, Amit Jain, H. Serhat Tetikol, Varun Jain, Mike Ruehle, Bryan Lajoie, Cooper Roddey, Severine Catreux, Rami Mehio, Mian Umair Ahsan, Qian Liu, Kai Wang, Sayed Mohammad Ebrahim Sahraeian, Li Tai Fang, Marghoob Mohiyuddin, Calvin Hung, Chirag Jain, Hanying Feng, Zhipan Li, Luoqi Chen, Fritz J. Sedlazeck, Justin M. Zook
Journal: Cell Genomics (2022)

The precisionFDA Truth Challenge V2 aimed to assess the state of the art of variant calling in challenging genomic regions. Starting with FASTQs, 20 challenge participants applied their variant-calling pipelines and submitted 64 variant call sets for one or more sequencing technologies (Illumina, PacBio HiFi, and Oxford Nanopore Technologies). Submissions were evaluated following best practices for benchmarking small variants with updated Genome in a Bottle benchmark sets and genome stratifications. Challenge submissions included numerous innovative methods, with graph-based and machine learning methods scoring best for short-read and long-read datasets, respectively. With machine learning approaches, combining multiple sequencing technologies performed particularly well. Recent developments in sequencing and variant calling have enabled benchmarking variants in challenging genomic regions, paving the way for the identification of previously unknown clinically relevant variants.
Lung Cancer in Serbia
Authors: Milena Cavic, Tomi Kovacevic, Bojan Zaric, Dejan Stojiljkovic, Natasa Jovanovic Korda, Milan Rancic, Radmila Jankovic, Davorin Radosavljevic, Goran Stojanovic, Jelena Spasic
Journal: Journal of Thoracic Oncology (2022)
Regression of EGFR positive established solid tumors in mice with the conditionally active T cell engager TAK-186
Authors: Danielle E Dettling, Eilene Kwok, Lucy Quach, Aakash Datt, Jeremiah D Degenhardt, Anand Panchal, Pui Seto, Jessica L Krakow, Russell Wall, Brian J Hillier, Ying Zhu, Maia Vinogradova, Robert B DuBridge, Chad May
Journal: Journal for ImmunoTherapy of Cancer (2022)

Despite clinical success with T cell engagers (TCEs) targeting hematological malignancies, achieving a safe and efficacious dose in patients with solid tumors remains challenging. Due to potency, low levels of target antigen expression on normal tissues may not be tolerated. To overcome this, we engineered a novel conditionally active TCE design called COBRA (Conditional Bispecific Redirected Activation). Administered as prodrugs, COBRAs bind to cell surface antigens on both normal and tumor tissues but are preferentially activated within the tumor microenvironment. A COBRA was engineered to target EGFR, TAK-186. The potency of precleaved TAK-186 relative to a non-cleavable control was assessed in vitro. Mice bearing established solid tumors expressing a range of EGFR levels were administered a single bolus of human T cells, and concurrently treated with TAK-186 and associated controls intravenously. We assessed the plasma and tumor exposure of intact and cleaved TAK-186. TAK-186 shows potent redirected T cell killing of antigen expressing tumor cells. In vivo efficacy studies demonstrate regressions of established solid tumors, dependent on intratumoral COBRA cleavage. Pharmacokinetic studies reveal TAK-186 is stable in circulation, but once activated is rapidly cleared due to loss of its albumin-binding half-life extension domain. The studies shown support the advancement of TAK-186, and the pursuit of additional COBRA TCEs for the treatment of solid tumors.
Appearance
Authors: Bonnie Salomon
Journal: Annals of Internal Medicine (2022)

Ad LibitumJune 2022AppearanceBonnie Salomon, MDBonnie Salomon, MDNorthwestern Medicine Lake Forest Hospital Lake Forest, IllinoisSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M21-3891 Audio Reading - “Appearance” Audio. Virginia L. Hood, MD, a physician from the University of Vermont, reads “Appearance” by Bonnie Salomon, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail She is seven. She has cancer.She has a portfor chemo in her small seven-year-old chest.She has a fever. She has cancer.I bend over to examine her and she eyesmy plastic hospital IDdangling from my lab coat.She points and says:You look different from your picture.In my picture I wear makeup.I had just done my hairso I could look professional,someone you could trustwith your seven-year-oldwho has cancer.She must have pictures, too,where she looks different.She takes off her scarf, lonely wisps of hairon a mostly bald seven-year-old head.and she has pointed out ... Author, Article, and Disclosure InformationAffiliations: Northwestern Medicine Lake Forest Hospital Lake Forest, IllinoisCorresponding Author: Bonnie Salomon, MD; e-mail, [email protected]com. PreviousarticleNextarticle Advertisement Audio Reading - “Appearance” Audio. Virginia L. Hood, MD, a physician from the University of Vermont, reads “Appearance” by Bonnie Salomon, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics June 2022Volume 175, Issue 6Page: 894 ePublished: 21 June 2022 Issue Published: June 2022 Copyright & PermissionsCopyright © 2022 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Cancer Deaths May Double by 2030 in Sub-Saharan Africa
Authors: Howard D. Larkin
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Novel gene therapy for rheumatoid arthritis with single local injection: adeno-associated virus-mediated delivery of A20/TNFAIP3
Authors: Qin Zhang, Fang-Xing Yu, Yang-Lin Wu, Cheng-Yuan Yang, Nai-Cheng Liu, Xu Zhu, Pi-Ming Zhao, Zhong-Ya Wang, Jun Lin
Journal: Military Medical Research (2022)
Elucidation of the genetic causes of bicuspid aortic valve disease
Authors: Jan Gehlen, Anja Stundl, Radoslaw Debiec, Federica Fontana, Markus Krane, Dinara Sharipova, Christopher P Nelson, Baravan Al-Kassou, Ann-Sophie Giel, Jan-Malte Sinning, Christopher M H Bruenger, Carolin F Zelck, Laura L Koebbe, Peter S Braund, Thomas R Webb, Simon Hetherington, Stephan Ensminger, Buntaro Fujita, Salah A Mohamed, Malakh Shrestha, Heike Krueger, Matthias Siepe, Fabian Alexander Kari, Peter Nordbeck, Larissa Buravezky, Malte Kelm, Verena Veulemans, Matti Adam, Stephan Baldus, Karl-Ludwig Laugwitz, Yannick Haas, Matthias Karck, Uwe Mehlhorn, Lars Oliver Conzelmann, Ingo Breitenbach, Corinna Lebherz, Paul Urbanski, Won-Keun Kim, Joscha Kandels, David Ellinghaus, Ulrike Nowak-Goettl, Per Hoffmann, Felix Wirth, Stefanie Doppler, Harald Lahm, Martina Dreßen, Moritz von Scheidt, Katharina Knoll, Thorsten Kessler, Christian Hengstenberg, Heribert Schunkert, Georg Nickenig, Markus M Nöthen, Aidan P Bolger, Salim Abdelilah-Seyfried, Nilesh J Samani, Jeanette Erdmann, Teresa Trenkwalder, Johannes Schumacher
Journal: Cardiovascular Research (2022)

The present study aims to characterize the genetic risk architecture of bicuspid aortic valve (BAV) disease, the most common congenital heart defect.
Yield of Head Computed Tomography Examinations for Common Psychiatric Presentations and Implications for Medical Clearance From a 6-Year Analysis of Acute Hospital Visits
Authors: Long H. Tu, Ajay Malhotra, Kevin N. Sheth, Reza Yaesoubi, Howard P. Forman, Arjun K. Venkatesh
Journal: JAMA Internal Medicine (2022)

This cross-sectional study uses single health system data on acute hospital visits over 6 years to determine the yield of head computed tomography examinations for actionable pathology in common psychiatric presentations and to characterize low-risk scenarios in which imaging may be avoidable.
Noncellular components in the liver cancer stem cell niche: Biology and potential clinical implications
Authors: Ka‐Hei Lam, Stephanie Ma
Journal: Hepatology (2022)

Cancer stem cells (CSCs) are now recognized as one of the major root causes of therapy failure and tumor recurrence in hepatocellular carcinoma (HCC). Early studies in the field focused primarily on the intrinsic regulators of CSC maintenance, but in recent years, mounting evidence has demonstrated the presence and role of extrinsic regulators in the tumor microenvironment (TME) in the control of liver CSCs. In addition to direct interaction with cellular components, noncellular components, including the extracellular matrix, hypoxia, nutrient deprivation, and secreted molecules within the tumor stroma and hepatitis viruses, also play a critical role in shaping the CSC niche. In this review, we highlight how various noncellular components in the TME play a role in regulating CSCs and how CSCs secrete components to interact with the TME to generate their own niche, working hand in hand to drive tumor physiology in HCC. In addition, we describe the potential clinical applications of these findings and propose perspectives on future research of noncellular components in the liver CSC niche.
Atypical Presentation of Isolated Gastric Variceal Bleeding Requiring Multidisciplinary Management
Authors: Kevin Litzenberg, Khalid Mumtaz, Gavisha Waidyaratne, Ahmad Anaizi, Mamdouh Khayat, Allan Tsung, Veronica Franco
Journal: Clinical Cardiology and Cardiovascular Interventions (2022)

Variceal bleeding is the most lethal manifestation of portal hypertension, most commonly due to esophageal varices in the setting of liver cirrhosis. Isolated gastric varices (IGV) are a rare cause of upper gastrointestinal bleeding, often of pancreatic origin. In this case we present a complex patient with a history of remote splenic injury leading to portopulmonary hypertension and the development of refractory bleeding due to IGV. We discuss the extensive multidisciplinary approach taken to provide comprehensive care and to control bleeding, which included endoscopic (sclerotherapy), radiologic (balloon-occluded antegrade transvenous obliteration [BATO] and splenic artery embolization) and surgical interventions (splenectomy).
Frequency of Ketoacidosis at Diagnosis of Pediatric Type 1 Diabetes Associated With Socioeconomic Deprivation and Urbanization: Results From the German Multicenter DPV Registry
Authors: Marie Auzanneau, Joachim Rosenbauer, Katharina Warncke, Werner Maier, Clemens Kamrath, Thomas Hofmann, Michael Wurm, Johanna Hammersen, Carmen Schröder, Kathrin Hake, Reinhard W. Holl
Journal: Diabetes Care (2022)

To investigate whether socioeconomic deprivation and urbanization are associated with the frequency of diabetic ketoacidosis (DKA) at diagnosis of pediatric type 1 diabetes.Children and adolescents aged ≤18 years, living in Germany, with newly diagnosed type 1 diabetes documented between 2016 and 2019 in the Diabetes Prospective Follow-up Registry (DPV; Diabetes-Patienten-Verlaufsdokumentation), were assigned to a quintile of regional socioeconomic deprivation (German Index of Socioeconomic Deprivation) and to a degree of urbanization (Eurostat) by using their residence postal code. With multiple logistic regression models, we investigated whether the frequency of DKA at diagnosis was associated with socioeconomic deprivation or urbanization and whether associations differed by age-group, sex, or migration status.In 10,598 children and adolescents with newly diagnosed type 1 diabetes, the frequency of DKA was lowest in the least deprived regions (Q1: 20.6% [95% CI 19.0-22.4], and increased with growing socioeconomic deprivation to 26.9% [25.0-28.8] in the most deprived regions [Q5]; P for trend <0.001). In rural areas, the frequency of DKA at diagnosis was significantly higher than in towns and suburbs (intermediate areas) or in cities (27.6% [95% CI 26.0-29.3] vs. 22.7% [21.4-24.0], P < 0.001, or vs. 24.3% [22.9-25.7], P = 0.007, respectively). The results did not significantly differ by age-group, sex, or migration background or after additional adjustment for socioeconomic deprivation or urbanization.This study provides evidence that prevention of DKA at diagnosis by means of awareness campaigns and screening for presymptomatic type 1 diabetes should particularly target socioeconomically disadvantaged regions and rural areas.